Maus, Mate ORCID: 0000-0002-2128-2479, Cuk, Mario, Patel, Bindi, Lian, Jayson, Ouimet, Mireille, Kaufmann, Ulrike, Yang, Jun, Horvath, Rita ORCID: 0000-0002-9841-170X, Hornig-Do, Hue-Tran, Chrzanowska-Lightowlers, Zofia M., Moore, Kathryn J., Cuervo, Ana Maria ORCID: 0000-0002-0771-700X and Feske, Stefan (2017). Store-Operated Ca2+ Entry Controls Induction of Lipolysis and the Transcriptional Reprogramming to Lipid Metabolism. Cell Metab., 25 (3). S. 698 - 713. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

Ca2+ signals were reported to control lipid homeostasis, but the Ca2+ channels and pathways involved are largely unknown. Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx pathway regulated by stromal interaction molecule 1 (STIM1), STIM2, and the Ca2+ channel ORAI1. We show that SOCE-deficient mice accumulate pathological amounts of lipid droplets in the liver, heart, and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 or ORAI1 show a similar phenotype, suggesting a cellintrinsic role for SOCE in the regulation of lipid metabolism. SOCE is crucial to induce mobilization of fatty acids from lipid droplets, lipolysis, and mitochondrial fatty acid oxidation. SOCE regulates cyclic AMP production and the expression of neutral lipases as well as the transcriptional regulators of lipid metabolism, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha), and peroxisome proliferator- activated receptor alpha (PPAR alpha). SOCE-deficient cells upregulate lipophagy, which protects them from lipotoxicity. Our data provide evidence for an important role of SOCE in lipid metabolism.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Maus, MateUNSPECIFIEDorcid.org/0000-0002-2128-2479UNSPECIFIED
Cuk, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patel, BindiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lian, JaysonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ouimet, MireilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufmann, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horvath, RitaUNSPECIFIEDorcid.org/0000-0002-9841-170XUNSPECIFIED
Hornig-Do, Hue-TranUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chrzanowska-Lightowlers, Zofia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, Kathryn J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cuervo, Ana MariaUNSPECIFIEDorcid.org/0000-0002-0771-700XUNSPECIFIED
Feske, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-236786
DOI: 10.1016/j.cmet.2016.12.021
Journal or Publication Title: Cell Metab.
Volume: 25
Number: 3
Page Range: S. 698 - 713
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACTIVATED RECEPTOR-ALPHA; ADENYLYL CYCLASES; FASTING RESPONSE; CALCIUM; AUTOPHAGY; ORAI1; STIM1; ADIPOSE; FAT; PHOSPHORYLATIONMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23678

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